Brain edema (also known as cerebral edema, brain oedema, cerebral oedema, brain swelling, or wet brain) is excess accumulation of fluid in the intracellular or extracellular spaces of the brain. Brain edema is broadly classified as vasogenic (movement of water and solutes across the blood brain barrier), or cytotoxic (osmotic swelling of cells in the affected area). In most instances, cytotoxic and vasogenic edema occur together. It is generally accepted that cytotoxic edema is dominant immediately following an injury or infarct, but gives way to a vasogenic edema that can persist for several days or longer.
Cytotoxic Edema in the brain is typically accompanied by brain swelling. Edema can result from almost any insult to the brain, including trauma, infarction, neoplasm, abscess, or conditions such as hypoxia or exposure to toxic compounds. Cytotoxic edema (also known as cellular edema, oncotic cell swelling, or oncosis) is a cellular process whereby extracellular Na+ and other cations are thought to enter into brain cells and accumulate intracellularly. The cation influx, in turn, drives influx of anions such as Cl−, which maintains electrical neutrality but generates an influx of water, resulting in cytotoxic edema through osmotic expansion of the cell. While the cytotoxic edema alone does not completely account for brain swelling, the formation of cytotoxic edema depletes the extracellular space of Na+, Cl−, and water, thereby creating a new gradient for these molecules across the capillary of the blood-brain barrier, thereby contributing to vasogenic edema. Cytotoxic edema evolves over minutes to hours and may be reversible, while the vasogenic phase occurs over hours to days, and is considered an irreversibly damaging process. Therefore, treatments to address cytotoxic edema in its early stages are desired. However, clinically acceptable strategies for management of brain edema have remained elusive, and available treatments are often of limited value for patients with brain edema. What is needed in the art are methods for the treatment of brain edema. The present invention provides methods of treating brain edema by inhibiting SLC26A11.